Table 2 PBC risk factors associated with female sex and ageing
From: Immunopathogenesis of primary biliary cirrhosis: an old wives' tale
Female Risk Factor | Significance |
|---|---|
Recurrent urinary tract infections | Molecular mimicry and cross reactivity with bacterial (such as E. coli) peptides and PDC-E2 epitopes |
Oestrogen deficiency | Increased propensity towards ductopaenia |
Increased incidence of vaginal infections | Alterations in vaginal flora increase the risk of developing urinary tract infections, which appear to play a role in PBC |
Ageing Risk Factors | Significance |
T cell membrane rigidity and decreased cell membrane fluidity | Alterations in T cell receptor signalling |
Decreased CD28 expression (especially in CD8+ cells) | Reduced regulatory T cell function and reduced immune response to infections |
Phenotypical alterations in CD8+ cells (such as increased CD127, and decreased CD39) | Decreased T regulatory cell function |
Increased telomere shortening from oxidative stress an ongoing inflammation | Increased cellular senescence, autophagy and apoptosis |
Increased senescence and autophagy | May contribute to exposure of self antigens to the immune system, as well as contributing to a pro-fibrotic and pro-inflammatory environment |
Increased apoptosis | Formation of apoptotic blebs (apotopes) increase exposure of mitochondrial antigens to the immune system |